Project Summary/Abstract The overall goal of the Gastrointestinal Cancers (GI) Program is to rapidly translate basic, population, and clinical research findings into more effective prevention and treatment strategies for patients with GI cancers. We have built a successful translational team through the close collaboration of GI clinical investigators with basic and population scientists. The Program is based on Team Science and, as a result, 27 members from nine academic departments in two schools are organized around the causes, prevention, and treatment of GI cancers, effectively facilitating bed to bench and bench to bedside research. Our clinician investigators are members of NCI task forces and PIs of national clinical trials in gastric, colon, and biliary cancer. Program members have $11M in peer-reviewed funding (direct costs), of which 45% is from NCI, 36% is from NIH, and 3% from other peer-reviewed funding sources. They interact regularly via a series of weekly and monthly seminars/meetings that facilitate exchange of recent research findings and interdisciplinary collaborations between Program investigators. These structured forums have fostered a large number of collaborative projects across the basic, population science, and clinical spectrum. During the last five years, the Program has generated 626 GI cancer related publications, of which 31% were inter-programmatic, 18% were intra- programmatic, and 50% inter-institutional. Heinz-Josef Lenz and Michael Kahn are Co-Leaders of the Program. Dr. Lenz is a physician-scientist internationally known for his work on pharmacogenomics and drug development in GI cancers. Dr. Kahn is a basic scientist and expert on signal transduction pathways and drug development. He is internationally known for his work in Wnt signaling, which has led to the development of the novel Wnt signaling modulator PRI-724, developed by Prism Pharma. PRI-724 completed a Phase Ia human clinical trial in 2012 and is currently in multiple Phase III trials. Other Program investigators have played pivotal roles in advancing the knowledge base in GI carcinogenesis and treatment outcomes. They include: 1) Stephen Gruber, an authority in colon cancer genetics and PI of the GWAS efforts in colon cancer; 2) Anthony El-Khoueiry and Syma Iqbal, who lead biomarker-driven clinical trials and early drug development in GI cancer; and 3) James Ou and Keigo Machida, who have made significant progress in understanding the role of HBV and HCV liver cancer and of tumor initiating cells in hepatocellular carcinoma. One of the strengths and signatures of the Program is that it has developed an infrastructure and a community of national and international collaborators that allow rapid transition of new findings from the bench into the clinic. The Program's scientific priorities, grant strategies, and clinical protocols are driven by the specific needs of our Los Angeles catchment area, focusing specifically on colorectal, cholangio, and gastric cancer in Hispanics, and hepatocellular carcinoma in Asians.